ABSTRACT
AimsBackgroundHeart murmurs in a new born are common due to transition from fetal circulation to neonatal circulation. Majority of these heart murmurs disappear in few days, but they can also be a sign of underlying congenital heart disease. In UK the practice in majority of neonatal units is, heart murmur in an asymptomatic new born with normal examination and passing pulseOx, is reviewed again by middle grade after 24 hours. If the murmur is innocent (Grade 1-2/6, no signs or symptoms) then baby is brought back to neonatal clinic in 4 -6 weeks for follow-up. Due to the Covid pandemic in March 2020 our unit policy changed for all innocent murmurs to be followed up by the GP at 6 – 8 weeks.ObjectiveTo assess the outcome of change in policy of heart murmur follow-up during the pandemic.MethodsA retrospective study from March 2020 – June 2021 (15 months). Data collected of infants who had a heart murmur on routine newborn examination, using NIPE Smart data, admission notes, Badger and postnatal notes. Infants discharged for GP follow up as per revised guideline were identified, and parents of these infants were contacted to enquire about GP follow up and the outcome.ResultsDuring the audit period, 101 infants were found to have a heart murmur on routine neonatal examination.Of these 101:• 72 had resolved on middle grade review after 24 hours• 11 received inpatient ECHO before discharge.• 18 were discharged for GP review at 6-8 weeks.17 of 18 parents of these infants were contacted, with one baby excluded due to incorrect data. 16 were aware of the heart murmur at the time of discharge.17/17 (100%) patients contacted had a GP review at 6-8 weeks as planned.At this review, the murmur persisted in 4/17 (24%) infants. One of these infants was re-reviewed by the GP and subsequently resolved, and a further two infants were referred to paediatrics for ECHO. The final infant was not referred or re-reviewed, but has remained clinically well.ConclusionAll infants discharged for GP follow up were reviewed, and all have remained clinically well since discharge. Murmur had resolved in the majority of infants. Where the murmur persisted, the infant was appropriately referred or re-reviewed in the majority of cases. Asymptomatic infants with low grade (likely innocent) murmurs, we can continue to discharge home with GP follow-up.
ABSTRACT
Understanding the immune response to severe acute respiratory syndrome coronavirus (SARS-CoV-2) is critical to overcome the current coronavirus disease (COVID-19) pandemic. Efforts are being made to understand the potential cross-protective immunity of memory T cells, induced by prior encounters with seasonal coronaviruses, in providing protection against severe COVID-19. In this study we assessed T-cell responses directed against highly conserved regions of SARS-CoV-2. Epitope mapping revealed 16 CD8+ T-cell epitopes across the nucleocapsid (N), spike (S), and open reading frame (ORF)3a proteins of SARS-CoV-2 and five CD8+ T-cell epitopes encoded within the highly conserved regions of the ORF1ab polyprotein of SARS-CoV-2. Comparative sequence analysis showed high conservation of SARS-CoV-2 ORF1ab T-cell epitopes in seasonal coronaviruses. Paradoxically, the immune responses directed against the conserved ORF1ab epitopes were infrequent and subdominant in both convalescent and unexposed participants. This subdominant immune response was consistent with a low abundance of ORF1ab encoded proteins in SARS-CoV-2 infected cells. Overall, these observations suggest that while cross-reactive CD8+ T cells likely exist in unexposed individuals, they are not common and therefore are unlikely to play a significant role in providing broad preexisting immunity in the community. IMPORTANCE T cells play a critical role in protection against SARS-CoV-2. Despite being highly topical, the protective role of preexisting memory CD8+ T cells, induced by prior exposure to circulating common coronavirus strains, remains less clear. In this study, we established a robust approach to specifically assess T cell responses to highly conserved regions within SARS-CoV-2. Consistent with recent observations we demonstrate that recognition of these highly conserved regions is associated with an increased likelihood of milder disease. However, extending these observations we observed that recognition of these conserved regions is rare in both exposed and unexposed volunteers, which we believe is associated with the low abundance of these proteins in SARS-CoV-2 infected cells. These observations have important implications for the likely role preexisting immunity plays in controlling severe disease, further emphasizing the importance of vaccination to generate the immunodominant T cells required for immune protection.